tbuckley/cabot-search huggingface dataset:
Influenza A virus use of BinCARD1 to facilitate the binding of viral NP to importin α7 is counteracted by TBK1-p62 axis-mediated autophagy
Authors: Xuyuan Wang, Li Jiang, Guangwen Wang, Wenjun Shi, Yuzhen Hu, Bo Wang, Xianying Zeng, Guobin Tian, Guohua Deng, Jianzhong Shi, Liling Liu, Chengjun Li, Hualan Chen
Journal: Cellular and Molecular Immunology (2022)

Abstract As a major component of the viral ribonucleoprotein (vRNP) complex in influenza A virus (IAV), nucleoprotein (NP) interacts with isoforms of importin α family members, leading to the import of itself and vRNP complex into the nucleus, a process pivotal in the replication cycle of IAV. In this study, we found that BinCARD1, an isoform of Bcl10-interacting protein with CARD (BinCARD), was leveraged by IAV for efficient viral replication. BinCARD1 promoted the nuclear import of the vRNP complex and newly synthesized NP and thus enhanced vRNP complex activity. Moreover, we found that BinCARD1 interacted with NP to promote NP binding to importin α7, an adaptor in the host nuclear import pathway. However, we also found that BinCARD1 promoted RIG-I-mediated innate immune signaling by mediating Lys63-linked polyubiquitination of TRAF3, and that TBK1 appeared to degrade BinCARD1. We showed that BinCARD1 was polyubiquitinated at residue K103 through a Lys63 linkage, which was recognized by the TBK1-p62 axis for autophagic degradation. Overall, our data demonstrate that IAV leverages BinCARD1 as an important host factor that promotes viral replication, and two mechanisms in the host defense system are triggered—innate immune signaling and autophagic degradation—to mitigate the promoting effect of BinCARD1 on the life cycle of IAV.
How covid-19 spreads: narratives, counter narratives, and social dramas
Authors: Trisha Greenhalgh, Mustafa Ozbilgin, David Tomlinson
Journal: BMJ (2022)

<b>Trisha Greenhalgh and colleagues</b> explore why inaccurate narratives about the mode of transmission of SARS-CoV-2 emerged early in the pandemic and shaped a flawed policy response, with tragic consequences
Physical Activity and Public Health
Authors: Russell R. Pate
Journal: JAMA (1995)

<h3>Objective.</h3> —To encourage increased participation in physical activity among Americans of all ages by issuing a public health recommendation on the types and amounts of physical activity needed for health promotion and disease prevention. <h3>Participants.</h3> —A planning committee of five scientists was established by the Centers for Disease Control and Prevention and the American College of Sports Medicine to organize a workshop. This committee selected 15 other workshop discussants on the basis of their research expertise in issues related to the health implications of physical activity. Several relevant professional or scientific organizations and federal agencies also were represented. <h3>Evidence.</h3> —The panel of experts reviewed the pertinent physiological, epidemiologic, and clinical evidence, including primary research articles and recent review articles. <h3>Consensus Process.</h3> —Major issues related to physical activity and health were outlined, and selected members of the expert panel drafted sections of the paper from this outline. A draft manuscript was prepared by the planning committee and circulated to the full panel in advance of the 2-day workshop. During the workshop, each section of the manuscript was reviewed by the expert panel. Primary attention was given to achieving group consensus concerning the recommended types and amounts of physical activity. A concise "public health message" was developed to express the recommendations of the panel. During the ensuing months, the consensus statement was further reviewed and revised and was formally endorsed by both the Centers for Disease Control and Prevention and the American College of Sports Medicine. <h3>Conclusion.</h3> —Every US adult should accumulate 30 minutes or more of moderate-intensity physical activity on most, preferably all, days of the week. (<i>JAMA</i>. 1995;273:402-407)
Purinergic Signaling during Inflammation
Authors: Holger K. Eltzschig, Michail V. Sitkovsky, Simon C. Robson
Journal: New England Journal of Medicine (2012)

Receptors for ATP and ADP and adenosine exert various effects. ATP and ADP signaling is mainly proinflammatory, and adenosine signaling is mainly antiinflammatory. Receptors for these nucleosides are emerging as therapeutic targets in a number of inflammatory and autoimmune diseases.
The Concepts of Stress and Stress System Disorders
Authors: George P. Chrousos
Journal: JAMA (1992)

<h3>Objective.</h3> —This article defines stress and related concepts and reviews their historical development. The notion of a stress system as the effector of the stress syndrome is suggested, and its physiologic and pathophysiologic manifestations are described. A new perspective on human disease states associated with dysregulation of the stress system is provided. <h3>Data Sources.</h3> —Published original articles from human and animal studies and selected reviews. Literature was surveyed utilizing MEDLINE and the<i>Index Medicus</i>. <h3>Study Selection.</h3> —Original articles from the basic science and human literature consisted entirely of controlled studies based on verified methodologies and, with the exception of the most recent studies, replicated by more than one laboratory. Many of the basic science and clinical studies had been conducted in our own laboratories and clinical research units. Reviews cited were written by acknowledged leaders in the fields of neurobiology, endocrinology, and behavior. <h3>Data Extraction.</h3> —Independent extraction and cross-referencing by the authors. <h3>Data Synthesis.</h3> —Stress and related concepts can be traced as far back as written science and medicine. The stress system coordinates the generalized stress response, which takes place when a stressor of any kind exceeds a threshold. The main components of the stress system are the corticotropin-releasing hormone and locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. There has been an exponential increase in knowledge regarding the interactions among the components of the stress system and between the stress system and other brain elements involved in the regulation of emotion, cognitive function, and behavior, as well as with the axes responsible for reproduction, growth, and immunity. This new knowledge has allowed association of stress system dysfunction, characterized by sustained hyperactivity and/or hypoactivity, to various pathophysiologic states that cut across the traditional boundaries of medical disciplines. These include a range of psychiatric, endocrine, and inflammatory disorders and/or susceptibility to such disorders. <h3>Conclusions.</h3> —We hope that knowledge from apparently disparate fields of science and medicine integrated into a working theoretical framework will allow generation and testing of new hypotheses on the pathophysiology and diagnosis of, and therapy for, a variety of human illnesses reflecting systematic alterations in the principal effectors of the generalized stress response. We predict that pharmacologic agents capable of altering the central apparatus that governs the stress response will be useful in the treatment of many of these illnesses. (<i>JAMA</i>. 1992;267:1244-1252)
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Diffuse large B-cell lymphoma (DLBCL) is recognized as a heterogeneous disease that can be cured in up to 60-70% of the cases with upfront therapy.However, relapsed/refractory DLBCL (R/R DLBCL) still represents a great clinical challenge.Palaz on-Carri on and colleagues conducted an open label multicenter phase 2 trial (R2-GDP-GOTEL) testing the synergism of combination lenalidomide (LEN) and rituximab (R2) plus gemcitabine, cisplatin, dexamethasone (R2-GDP schedule) in R/R DLBCL patients, not suitable for autologous stem cell transplantation.Results suggest that LEN in combination with R-GDP (R2-GDP schedule) is an immunomodulatory treatment option with manageable toxicity and promising clinical activity, with high proportion of complete responses and favorable survival outcomes in patients with R/R DLBCL.Additionally, evolution of MDSC and Treg in peripheral blood seem an alternative for monitoring immune profiling that is related to clinical outcomes of overall survival and complete responses.
Transmission of Strongyloidiasis by Kidney Transplant?
Authors: Wendy E. Hoy
Journal: JAMA (1981)

DISSEMINATED strongyloidiasis has been described in renal transplant patients<sup>1</sup>and the life cycle of the parasite has been reviewed. It is generally supposed that immunosuppression allows activation and clinical expression of a preexisting<i>Strongyloides</i>infestation in the recipient. We report the development of strongyloidiasis in two renal transplant patients who received their allografts from the same cadaveric donor. We were unable to find definite evidence of<i>Strongyloides</i>infestation in the autopsy tissue from the donor but submit that the infection may have been transmitted to the recipients with the kidneys at transplantation. <h3>Report of Cases</h3><h3>The Donor.—</h3> A 47-year-old man suffered a subarachnoid hemorrhage. He had no known medical problems except a "tendency toward diabetes" and no reported gastrointestinal illness. He had been born and raised in the northeastern United States and had worked for more than 20 years as an insulation engineer for a local company. He had
A Controlled Trial of Combined Therapy for Newly Diagnosed Severe Childhood IgA Nephropathy
Authors: NORISHIGE YOSHIKAWA, HIROSHI ITO, TADASU SAKAI, YASUO TAKEKOSHI, MASATAKA HONDA, MIDORI AWAZU, KATSUMI ITO, KIKUO IITAKA, YASUSHI KOITABASHI, KANJI YAMAOKA, KIMIKO NAKAGAWA, HAJIME NAKAMURA, SOUICHIROU MATSUYAMA, YOSHIKI SEINO, NOBUAKI TAKEDA, SHINZABUROU HATTORI, MAKOTO NINOMIYA
Journal: Journal of the American Society of Nephrology (1999)

The most appropriate treatment for patients with IgA nephropathy is controversial. Treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole early in the course of disease may prevent immunologic renal injury in children with severe IgA nephropathy. To determine whether similar results can be obtained with a combination of just heparin-warfarin and dipyridamole, the effects of such treatment were compared to those of treatment with prednisolone, azathioprine, heparin-warfarin, and dipyridamole in 78 children with newly diagnosed IgA nephropathy showing diffuse mesangial proliferation. The patients were randomly assigned to receive either prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr (group 1) or heparin-warfarin and dipyridamole for 2 yr (group 2). All of the 40 patients in group 1 and 34 of the 38 patients in group 2 completed the trial. The mean urinary protein excretion fell in group 1 patients (P < 0.0001), but remained unchanged in group 2 patients. The mean serum IgA concentration was reduced in group 1 patients (P = 0.0002), but was unchanged in group 2 patients. BP and creatinine clearance were normal at the end of the trial in all but one group 2 patient, who developed chronic renal insufficiency. The percentage of glomeruli showing sclerosis was unchanged in group 1 patients, but increased in group 2 patients (P = 0.006). The intensity of mesangial IgA deposits decreased in group 1 patients (P = 0.02), but remained unchanged in group 2 patients. In conclusion, the present study shows that treatment of children with severe IgA nephropathy with prednisolone, azathioprine, heparin-warfarin, and dipyridamole for 2 yr early in the course of disease reduces immunologic renal injury and prevents increase of sclerosed glomeruli.
Diuresis Renography
Authors: MONICA A. ROSSLEIGH, DIANE M. LEIGHTON, ROBERT H. FARNSWORTH
Journal: Clinical Nuclear Medicine (1993)

ROSSLEIGH, MONICA A. MBBS, (Hons) FRACP.; LEIGHTON, DIANE M. MB ChB, FRACR; FARNSWORTH, ROBERT H. MBBS, FRCS (Ed), FRCM Author Information
Highly bright aggregation-induced emission nanodots for precise photoacoustic/NIR-II fluorescence imaging-guided resection of neuroendocrine neoplasms and sentinel lymph nodes
Authors: Ruitong Xu, Di Jiao, Qin Long, Xiaolin Li, Ke Shan, Xianglong Kong, Hanlin Ou, Dan Ding, Qiyun Tang
Journal: Biomaterials (2022)
RARγ: The Bone of Contention for Endothelial Cells in Prostate Cancer Metastasis
Authors: Snigdha Bhowmick, Neil A. Bhowmick
Journal: Cancer Research (2022)

Excessive bone deposition associated with prostate cancer bone metastases is believed to aid in metastatic progression. One mechanism of osteoblast expansion is the transdifferentiation of bone marrow endothelial cells. Prostate cancer cells contribute several secreted factors, including bone morphogenetic protein 4 (BMP4), to the microenvironment that support osteoblastic transdifferentiation. In this issue of Cancer Research, Yu and colleagues share their findings of how BMP-mediated endothelial conversion can be inhibited by treatment with retinoic acid receptor (RAR) agonists. Using agonists like the all-trans retinoic acid or palovarotene, the authors demonstrated the role of the interaction of BMP-activated SMAD1 with RARγ for osteoblastic differentiation. RARγ agonists potentiated the proteasomal degradation of the Smad1–RARγ complex, blocking BMP signaling. Because palovarotene is clinically effective in the treatment of aberrant bone formation found in fibrodysplasia ossificans progressiva, its repurposing for the treatment of osteoblastic cancer metastasis is promising. However, patient selection and dose-finding studies will be critical for the translation of these findings to complement standard of care for patients with bone metastatic prostate cancer. See related article by Yu et al., p. 3158
PRC2 Loss and DNMT Inhibition Boost Viral Mimicry in Cancer
Authors: Sonia Guil, Manel Esteller
Journal: Cancer Discovery (2022)

Summary: In this issue of Cancer Discovery, Patel and colleagues explore the synergistic lethality of PRC2 inactivation and DNMT inhibition in malignant peripheral nerve sheath tumor cells. Reactivation of retrotransposons under this dual control suggests that the viral mimicry response contributes to enhanced cytotoxicity with potential clinical implications. See related article by Patel et al., p. 2120 (5).
Why ARNT Prostate Tumors Responding to Enzalutamide?
Authors: Meng Zhang, Thaidy Moreno-Rodriguez, David A. Quigley
Journal: Cancer Discovery (2022)

Summary: Prostate tumors can develop resistance to androgen receptor (AR)–targeted therapies through treatment-induced changes in transcription factor activity that promote transcriptional and morphologic features of a neuroendocrine lineage. This study identifies an unexpected role for the circadian protein ARNTL in resistance to enzalutamide, a second-generation AR-targeted therapy. See related article by Linder et al., p. 2074 (4).
A prospective study of risk factors associated with seroprevalence of SARS-CoV-2 antibodies in healthcare workers at a large UK teaching hospital
Authors: Daniel J Cooper, Sara Lear, Laura Watson, Ashley Shaw, Mark Ferris, Rainer Doffinger, Rachel Bousfield, Katherine Sharrocks, Michael P. Weekes, Ben Warne, Dominic Sparkes, Nick K Jones, Lucy Rivett, Matthew Routledge, Afzal Chaudhry, Katherine Dempsey, Montgomery Matson, Adil Lakha, George Gathercole, Olivia O'Connor, Emily Wilson, Orthi Shahzad, Kieran Toms, Rachel Thompson, Ian Halsall, David Halsall, Sally Houghton, Sofia Papadia, Nathalie Kingston, Kathleen E Stirrups, Barbara Graves, Paul Townsend, Neil Walker, Hannah Stark, Daniela De Angelis, Shaun Seaman, Gordon Dougan, John R Bradley, M. Estée Török, Ian Goodfellow, Stephen Baker
Journal: Journal of Infection (2022)
Correction: Cross-talk Signaling between HER3 and HPV16 E6 and E7 Mediates Resistance to PI3K Inhibitors in Head and Neck Cancer
Authors: Toni M. Brand, Stefan Hartmann, Neil E. Bhola, Hua Li, Yan Zeng, Rachel A. O'Keefe, Max V. Ranall, Sourav Bandyopadhyay, Margaret Soucheray, Nevan J. Krogan, Carolyn Kemp, Umamaheswar Duvvuri, Theresa LaVallee, Daniel E. Johnson, Michelle A. Ozbun, Julie E. Bauman, Jennifer R. Grandis
Journal: Cancer Research (2022)

In the original version of this article (1), there are errors in Figs. 2C and 4E and Supplementary Fig. S3. The authors inadvertently used the same image for p70S6K in SCC47 and SCC90 cells in Fig. 2C. The image of p-AKT-T308 in 93-VU-147T cells in Fig. 3A was duplicated in Supplementary Fig. S3A for p-AKT-T308 in 93-VU-147T cells. The same image was also used for E6 in the PDX-1 and PDX-3 models in Fig. 4E. In addition, a duplicated image was provided for p-AKT-S473 and p-AKT-T308 in SCC90 cells in Supplementary Fig. S3A. The correct original images have been provided, and the errors have been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.Additional duplications were detected in Fig. 1D, 1F, and Fig. 3D, but the authors were unable to furnish the original data pertaining to those panels, which remain unchanged in the current versions. The editors have therefore addressed those issues in a separate Editor's Note (2).
Highlights from Recent Cancer Literature
Journal: Cancer Research (2022)

Stepwise Genome Editing to Model Tumor DevelopmentCancer type-specific mutations are common, and their stepwise alteration has been shown for tumors including melanoma and colorectal cancer.Hodis and colleagues started with primary human melanocytes and used precise genome editing to introduce up to five sequential mutations occurring in melanoma.Nine unique melanoma models were generated by introduction of mutations affecting six different pathways: CDKN2A (RB pathway), BRAF (MAPK), TERT (telomerase), PTEN (PI3K/AKT), TP53 (p53), and APC (WNT).In these models, melanocyte genotypes were linked to phenotypes including proliferation, cancer-associated gene expression programs in vitro, as well as rapid tumor growth, tumor pigmentation, and metastasis in vivo.Notably, the authors demonstrated that the melanoma-specific mutations also affected the composition of the tumor microenvironment.Importantly, the melanoma models mimicked gene expression programs found in patient tumors.Expert Commentary: Sequential introduction of cancer type-specific mutations using genome editing may be a powerful approach to study progressive cancer development.
Pumping Iron: Ferritinophagy Promotes Survival and Therapy Resistance in Pancreatic Cancer
Authors: Vaibhav Jain, Ravi K. Amaravadi
Journal: Cancer Discovery (2022)

Summary: Autophagy is an adaptive response to metabolic and therapeutic stress, especially in treatment-refractory cancers such as pancreatic cancer. In this issue of Cancer Discovery, two groups establish ferritinophagy, a selective autophagy program that could become a drug target, as the mechanism that pumps iron into mitochondria via the lysosome, enabling survival and therapy resistance in pancreas cancer. See related article by Santana-Codina et al., p. 2180 (3). See related article by Ravichandran et al., p. 2198 (4).
Editor's Note: Cross-talk Signaling between HER3 and HPV16 E6 and E7 Mediates Resistance to PI3K Inhibitors in Head and Neck Cancer
Authors: Toni M. Brand, Stefan Hartmann, Neil E. Bhola, Hua Li, Yan Zeng, Rachel A. O'Keefe, Max V. Ranall, Sourav Bandyopadhyay, Margaret Soucheray, Nevan J. Krogan, Carolyn Kemp, Umamaheswar Duvvuri, Theresa LaVallee, Daniel E. Johnson, Michelle A. Ozbun, Julie E. Bauman, Jennifer R. Grandis
Journal: Cancer Research (2022)

The editors are publishing this note to alert readers to a concern about this article (1). An investigation into this article was performed by The University of California San Francisco's Office of Ethics and Compliance. In Fig. 1D, the same image was used for the AKT panel for SCC2 and SCC90 cells and the rpS6 panel for SCC152 and 93-Vu-147 cells. Also, the image provided for the p-AKT-S473 blot for HPV(+): PDX-1 in Fig. 1F is duplicated with the HER3 blot for HPV(+): PDX-1 in Fig. 3D. Because satisfactorily corrected figures with original data could not be provided, the editors are publishing this note to make readers aware of these concerns.Additional duplications were detected in Figs. 2C and 4E and Supplementary Fig. S3, and the authors provided original data pertaining to those panels. The Editors have therefore corrected those figures in the latest online HTML and PDF versions of the article and have addressed those issues in a separate Correction Notice (2).
Incidence and factors predictive of recurrent thrombosis in people with non-cirrhotic portal vein thrombosis
Authors: Anna Baiges, Bogdan Procopet, Gilberto Silva-Junior, Elba Llop, Luis Tellez, Anna Darnell, Ángeles Garcia-Criado, Fanny Turon, Oana Nicoara-Farcau, Carlos González-Alayón, Hélène Larrue, Marta Magaz, Pol Olivas, Valeria Perez-Campuzano, Jose Luis Calleja, Agustin Albillos, Juan Carlos Reverter, Christophe Bureau, Jaime Bosch, Virginia Hernández-Gea, Juan Carlos Garcia-Pagán
Journal: Journal of Hepatology (2022)